Bleeding in patients on concurrent treatment with a selective serotonin reuptake inhibitor (SSRI) and low-dose acetylsalicylic acid (ASA) compared with SSRI or low-dose ASA alone-A systematic review and meta-analysis.

Aims: The aim of this study was to systematically review whether concurrent treatment with an SSRI and low-dose ASA increases the risk of bleeding compared with treatment with an SSRI alone or ASA alone.

Methods: Medline, Embase, the Cochrane Library, PsycINFO and Web of Science (from database inception to January 2023) were searched according to PICO: P = patients on treatment with an SSRI and/or low-dose ASA; I = intervention: SSRI + ASA; C = comparison: ASA or SSRI alone; O = outcomes: bleeding/major bleeding. The included articles were assessed using checklists. Studies without major risk of bias formed the basis for the conclusions. Extracted data were pooled using random-effects meta-analyses. Certainty of evidence was assessed according to GRADE.

Results: Twenty-four studies met the PICO and were included. One randomized and six nonrandomized studies were assessed not to have major risk of bias. Regarding SSRI + ASA vs. ASA only, the pooled hazard ratio of three nonrandomized studies (n = 38 467) was 1.37 (95% confidence interval: 1.10; 1.70; I = 0%), and the pooled odds ratio of two nonrandomized studies (n = 28 296) was 0.95 (0.77; 1.19; I = 0%). Regarding SSRI + ASA vs. SSRI only, the randomized controlled trial (n = 1048) reported a hazard ratio of 1.82 (0.66; 5.02), the hazard ratio being 1.60 (1.24; 2.06) for ASA vs. placebo in patients without SSRI treatment; and one nonrandomized controlled study (n = 18 920) reported an incidence rate ratio of 1.03 (0.96; 1.12).

Conclusions: The compiled evidence was too uncertain to support an interaction when an SSRI is added to low-dose ASA. Low-dose ASA added to an SSRI may imply an increased risk of bleeding primarily attributable to the initiation of ASA.